K9 and equine joint health food supplement and method of administering

ABSTRACT

Kolla2 powder compositions, methods of preparing the compositions, and use of the compositions in treating degenerative joint diseases, joint defects, hip displasia, and osteoarthritis. The compositions are orally administered to K9&#39;s and equines in need of cartilage cell repair in a daily dietary food supplement.

CROSS REFERENCE TO RELATED APPLICATION

This application is a Continuation-in-Part of U.S. Ser. No. 09/768,141, filed on Jan. 24, 2001, and the disclosure of which is incorporated herein by reference to the extent necessary to a fully and complete enabling disclosure of this present invention.

FIELD OF THE INVENTION

The present invention provides a composition useful as a dietary food supplement for treating existing or incipient or prospective arthritis by oral consumption of the food supplement by mammals. Particularly, the present invention provides a composition, method of making, and method of using, which is particularly useful in preventing, delaying, or treating arthritis and other joint health maladies in mammals including dogs (i.e., K9's) and horses (i.e., equines). The inventive composition and method of use provides for extraction from desiccated avian sternal cartilage of collagen type II powder, a method of manufacturing the composition, and its use as a food supplement believed to have salutary and beneficial effects in the prevention, delay, and/or relief of arthritis and other joint conditions, as a therapeutic agent, and as a nutritional food supplement.

BACKGROUND OF THE INVENTION

One of every 3 Americans over the age of 60 suffers from osteoarthritis. It results from the natural wear and tear of joint cartilage. As mammals age, the body's ability to make the protein type II collagen slows down. This protein type II collagen is the protein needed to maintain and rebuild cartilage tissue. Collagen is a complex structural protein, which provides strength and flexibility to all connective tissues. Collagen is a major component of muscles, tendons, cartilage, ligaments, joints and blood vessels. There are four main types of collagen: types I, II, III, and IV. Types I and III are primarily found in skin, tendon and bone. In contrast, collagen type II is found predominately in articulator cartilage.

Collagen is an unusual protein, in that the proportion of glycine residues is nearly one-third which is unusually high. Proline is also present to a much greater extent in collagen that in most other proteins. Moreover, collagen contains two amino acids, 4-hydroxyproline and 5-hydroxylysine, that are found in very few other proteins. The amino acid sequence of collagen is remarkably regular, nearly every third amino acid is glycine. In addition, the sequence of glycine-proline-hydroxyproline recurs frequently. In contrast, globular proteins rarely exhibit regularities in their amino acid sequences (Stryer. L., Biochemistry, Third Edition, W.H. Freeman and Co., New York, 1988, pp. 262).

Humans are not the only mammals who suffer from degenerative joint conditions and diseases. In particular, dogs (i.e., K9's) and horses (i.e., equines) both suffer from joint conditions which impact their quality of life. Particularly large breed dogs commonly suffer from a condition known as hip joint displasia. Hip displasia in dogs accounts for over 30% of all orthopedic cases in veterinary practice, according to the Orthopedic Foundation for Animals (OFA).

In the normal K9 hip joint, the acetabular cup of the hip joint is deep and has a thick healthy cartilage. The head of the femur sits tightly into the acetabulum. On the other hand, hip displasia in the K9 is characterized by an angulation of the femoral head and other associated joint malformations. That is, hip displasia is a developmental disorder affecting the coxofemoral (hip) joints in dogs. The problems associated with hip displasia stem from an imbalance in the muscle mass and mechanical forces which are centered on the hip joint. This imbalance is associated with excessive laxity (looseness) which is usually the result of a shallow acetabulum (cup). When the hip joints exhibit laxity (looseness), the ball of the femur rides on the edge of the socket rather than gliding smoothly in the socket. This results in pain and eventually to the formation of abnormal calcium deposits, bone spurs and/or arthritis. Eventually, some hip joints will suffer either a partial or complete subluxation (i.e., displacement of the femoral head from the cup of the acetabulum.

Continued use of the affected joint causes abnormal wear on the joint's cartilage surfaces leading to further damage and a self-perpetuating degenerative process ensues. Abnormal bony development of the hip joint often results, and inflammation and irritation (arthritis) ultimately cause mild to severe lameness. The joint capsule becomes inflamed and a subsequent increase in synovial fluid in the joint exacerbates the laxity. These physiological changes should be dealt with early (between 4 and 8 months) to attempt to reduce the progress toward degenerative joint disease. The hallmark sign of degenerative joint disease is articular cartilage damage. This results in the exposure of subchondral bone and pain nerve fibers resulting in significant joint pain. Once degenerative joint disease is present, there a fewer treatment options available.

In horses (i.e., equine), the joint disorders frequently result from overuse, and over-training. That is, thoroughbred horses frequently are subjected to a rigorous training regimen from an early age, and this subjects the animals joints to great stresses. With joint deterioration progressing generally according to the amount of use and stress, it is to be expected that these animals will eventually experience joint deterioration and disease.

In 1986, collagen was sold for the first time in the United States for use as a food supplement. Collagen (a mixture of type I and type III) was extracted from calf skin tissue, and prepared in powder form for use as a dietary supplement. In 1987, the composition was sold compressed into 1,000 mg. tablets which comprised collagen powder and 10 mg. Vitamin C.

U.S. Pat. No. 4,804,745 to Koepff et al. discloses agents containing collagen peptides produced by enzymatic hydrolysis for the treatment of degenerative joint diseases. These peptides can be obtained from animal skin, animal bones and other sufficiently purified connective tissue and have average molecular weights of between 30 and 45 kilodaltons.

U.S. Pat. No. 5,399,347 to Trentham et al. and Trentham et al. (Science 261:1727-1729, 1993) disclose the treatment of rheumatoid arthritis (RA) with water-soluble whole chick collagen type II or biologically active peptides derived therefrom. The mechanism by which the effect is believed to occur is via oral tolerization.

U.S. Pat. No. 5,364,845 to Henderson discloses a therapeutic composition and method for the protection, treatment and repair of connective tissue in mammals. This composition comprises glucosamine, chondroitin sulfate and manganese ascorbate. U.S. Pat. No. 5,587,363 to Henderson discloses a therapeutic composition and method for the protection, treatment and repair of connective tissue in mammals which includes aminosugars and glycosaminoglycans.

U.S. Pat. No. 6,025,327 to Alkayali discloses a therapeutic composition and method for the protection, treatment and repair of joint cartilage in mammals. This composition comprises hydrolyzed collagen type II water-soluble, denatured collagen type II obtained from chicken sternal cartilage.

SUMMARY OF THE INVENTION

The present invention provides a desiccated avian sternal cartilage collagen type II powder, the powder having an average molecular weight of between about 45,000 and 65,000 daltons. Preferably, the powder has an average molecular weight of about 50,000 daltons. In one aspect of this preferred art, the powder is obtained from desiccated young avian sternal cartilage. Preferably, the avian sternal cartilage is collected from 4-8 week old chicks. The powder is partially water-soluble and the composition comprises 20% to 30% mucopolysaccaride (carbohydrate) and 65% to 70% collagen type II (protein) and the content of 1% to 3% lipids is part of the powder composition. The present invention also provides a method of helping cartilage formation in mammals with connective tissue disorders and degenerative joint diseases, comprising orally administering to the individual an effective daily cartilage-inducing amount of the powder.

The degenerative joint diseases include cartilage injuries, joint defects, rheumatoid arthritis, osteoarthritis, vascular disease, polychondritis, and connective tissue disorder. Preferably, the effective daily dosage amount is between about 600 mg. and 10,000 mg. More preferably, the effective daily dosage amount is between about 1,200 mg. and 7,200 mg. Most preferably, the effective daily dosage amount is between 2,400 mg. and 3,600 mg. Another aspect of the invention is a method of providing the inventive material as a preventative nutritional supplement, comprising orally administering to an individual a daily dosage of the inventive material having an average molecular weight of between about 45,000 and 65,000 daltons.

Particularly, the applicant has determined and discovered that the administration of the present inventive material to dogs and horses as a food supplement is particularly effective both in the prevention and the remediation of degenerative joint conditions as outlined above.

Still another embodiment of the invention is a method of preparing the inventive material, comprising the following steps: cutting fresh 4 to 8 weeks young chicken sternal cartilage to within not less than about 2 mm of the bone; grinding cartilage into ground mesh, suspending ground cartilage in an aqueous solution; sterilizing said cartilage, filtering the ground cartilage, defatting the ground cartilage, drying the ground cartilage, milling the dried cartilage to form desiccated sternal avian cartilage powder.

The method may further comprise the step of deep freezing the cartilage after cutting step. Preferably, the aqueous solution is water. Advantageously, grinding the deep frozen cartilage into ground mesh. In one aspect of this preferred embodiment, the sterilization process step comprises a temperature control at a minimum of 95° C. for a minimum of 30 minutes. Preferably, the drying step comprises a temperature control at a minimum 95° C. for a minimum of 6 hours. Preferably, the milling into powder and the bulk density at 20° C. is approximately about 600 g/l.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a schematic diagram of the process for preparing and the manufacturing of the desiccated sternal avian cartilage powder of the invention;

FIG. 2 is a line drawing of a normal K9 hip joint;

FIG. 3 is a line drawings of an early/mild-stage displasic K9 hip joint;

FIG. 3A is a print of a radiograph (i.e., an x-ray) of a young (i.e., less than one year of age) large breed K9 with degenerative joint disease of the hip, a precursor to hip displasia, taken in July 1999;

FIG. 4 is a copy of an x-ray of the same K9 seen in FIG. 3A, taken substantially 7 years after the x-ray of FIG. 3A;

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS OF THE INVENTION

The present invention provides a desiccated avian sternal cartilage denatured collagen II protein composition, a method for preparing the composition, and methods for use of the composition in the treatment and repair of cartilage defects, and for the prevention of arthritis diseases. Particularly, the applicant has determined and discovered that particular benefit may be obtained in the prevention and remediation of degenerative joint conditions as outlined above in both K9's and in equines.

The method involves cutting fresh sternal cartilage from 4 to 8 weeks avian carcasses and removing all meat, blood and bone therefrom. The sternal cartilage is cut leaving a space of about two and a half millimeters from the bone so as to not remove any bone fragments. This is essential to the purity of the final product because it avoids contamination of collagen type II protein with types III and I found in bone. The fresh sternal cartilage is then promptly deep-frozen and the remained of the chicken carcass is discarded. It is important the sternal cartilage, cut so no bone is included, that is used for preparing the powder.

The sternal cartilage is processed according to good manufacturing practice (GMP). Other contemplated sources of collagen type II are mammalian (i.e. bovine and porcine) and shark fins.

The production of desiccated avian sternal cartilage in powdered form is shown in FIG. 1. Ground deep-frozen cartilage is suspended in an aqueous solution, preferably water, and sterilized at temperature control at about 95° C. for a minimum of 30 minutes. The water is removed by filtration and cartilage mesh is treated with ethanol to remove excess fat, filtration and drying the sternal cartilage at a temperature between about 95° C. for a minimum of 6 hours. The dried sternal cartilage is milled to a fine mesh powdered, preferably bulk density at 20° C. is approximately about 600 g/l. The powder is packed in a 50 kg, drum with a plastic bag liner. The powder is partially water-soluble.

The average molecular weight of the final powder is between 45,000 and 65,000 daltons, preferably 50,000 daltons. The final powder product is 20% to 30% mucopolysaccharides, particularly chondroitin sulfate and glucosamine sulfate. The product has 375 calories per 100 grams, contains 65% collagen type II protein (13.1 total nitrogen), and 20% carbohydrate and 2% lipids. The powder is ready to be utilized after the human body's superior natural enzyme break down the amino acid chain into the precise genetic code for joint cartilage repair. The natural lipids found in the powder of the invention together with collagen II protein and carbohydrates constitute the chief structural components of joint cartilage cell. The unique amino acid composition and molecular weight of the powder differs substantially from typical collagen proteins and is shown in Table 1. Tryptophan and hydroxylysine amino acids are absent and hydroxyproline is low. The molecular weight and amino acid composition and the natural lipids which is essential to promote optimal assimilation of the peptides. TABLE 1 Amino acid composition of the invention Amino acid g/100 g product arginine 4.42 alanine 4.51 asparagine/aspartic acid 5.29 cystine 0.46 glutamine/glutamic acid 8.75 glycine 8.93 histidine 2.05 hydroxyproline 3.90 isoleucine 1.90 leucine 4.20 lysine 3.54 methionine 1.38 phenylalanine 2.14 proline 5.25 serine 2.45 threonine 2.60 tyrosine 1.15 valine 2.43

When the inventive material, preferably in the form of a powder, administered in capsules or in compressed tablets, is taken orally as a daily dietary supplement by an individual with a degenerative joint disorder, the invention helps that individual fabricate cartilage and considerably improves the joint disorder. “Oral” administration includes oral, enteral or intragastric administration. The invention can be used to treat, for instance, degenerative joint disease (i.e. rheumatoid arthritis), osteoarthritis, cartilage injuries, joint defects, connective tissue disorder, polychondritis, autoimmune diseases involving connective tissue autoantibodies (i.e. rheumatoid arthritis), and any other connective tissue disorder which would benefit from increased synthesis of cartilage.

Particularly, as is outlined below, the applicant has discovered and determined that administration orally of the inventive material over an extended period of time is effective in the prevention and/or remediation of degenerative joint disorders in both K9's and equines (i.e., dogs and horses). Referring now to FIG. 2, it is seen that in the normal K9 hip joint 10, the femoral head 12 (i.e., the ball of the hip joint) is disposed at an angle approaching 75 to 80° relative to the shaft 14 of the femur. The acetabular cup 16 is deep, and healthy cartilage, indicated by arrowed numeral 18, is present in the cup and on the ball of the femur. The head of the femur 12 sets tightly within the acetabulum.

In contrast, viewing FIG. 3, a K9 case of early/mild displasic hip with no degenerative changes is illustrated. Note how joint laxity allows the head 20 of the femur 22 to subluxate (i.e., move to some extent outwardly of the acetabular cup, rather than being held deeply into the acetabular cup). The acetabular cup 24 may be abnormally shallow and the joint may exhibit laxity. This stage of hip displasia will often be treated with corrective surgery before the disease progresses—requiring more invasive and costly surgery.

However, attention now to FIG. 3A shows a radiograph of a young large breed K9 at an age of less than one year with a hip joint condition substantially as shown in FIG. 3. Note particularly in the circled area, illustrating the left hip joint, the apparent condition of joint laxity. The animal was just beginning to show early signs of the hip displasia condition. That is, the animal was sporadically but increasingly refusing to bear weight on the hips, or to show normal energetic activity. A veterinary examination (including this x-ray of FIG. 3A) led to a diagnosis of bilateral incongruity of the hip joints. Angulation of the femoral heads was noted, and some uncovering of the acetabulum was also noted. A recommendation to begin steroid therapy and to consider surgical correction was given.

However, FIG. 4 shows this same animal after essentially 7 years of supplementation with the present inventive joint health food supplement. As FIG. 4 shows, there has been no progression of the hip displasia. Note particularly in the circled area of FIG. 4, also illustrating the left hip joint, that there is no apparent progression in the condition of joint laxity. In fact a veterinary examination of this animal conducted in February of 2006 (including the x-ray seen as FIG. 4) led to a diagnosis of minimal hip displasia, with essentially zero changes in comparison to the condition of the animal in 1999 (recalling FIG. 3A).

In addition to the above, the applicant has administered the inventive food supplement to other K9's on a trial basis in order to assess the efficacy of the food supplement. In one case, the food supplement was assessed by DMV. J. Schreiber, on his patent “Paco.” Paco is a small breed dog, an overweight three-legged Chihuahua, with osteoarthritis of the stifle joints, resulting in the dog being a semi-invalid. This animal was born without a front leg. The dog's age at the time of evaluation of the present inventive food supplement was 7½ years, and after using the inventive food supplement for an interval of 6 months, Dr. Schreiber reported a remarkable difference in the animal's behavior, with the dog being able to move about and even jump. The dog's comfort level was improved at least 75% in the opinion of Dr. Schreiber.

The applicant also participated with the Agura Animal Shelter of Agura, Calif., in an evaluation of the inventive food supplement on several older dogs where were resident at the shelter. When an older dog was noticed to suffer from stiffness of the limbs, they were started on a supplementation program using the present inventive food supplement. In all reported cases, the Agura Animal Shelter reported that the animals were able to move about with increased comfort, and no signs of stiffness. The Shelter reported that the inventive food supplement allowed the senior dogs to be more comfortable while at the Shelter, but also helped to make these dogs more viable as adoption candidates.

For oral administration as a nutritional dietary supplement, therapeutic or prophylactic agent, the inventive food supplement may be provided as a dispersible powder or granule, tablet, hard or soft capsule, emulsion, aqueous or oil suspension, syrup or elixir. Compositions intended for oral use may be prepared in accordance with any method known in the art for the manufacturing of nutritional supplement compositions and such compositions may contain one or more of the following components: preservatives, sweeteners, flavoring agents and coloring agents. The flavoring agents and sweetening will enhance the palatability of the preparation.

Tablets containing the invention in admixture with non-toxic pharmaceutically acceptable excipients suitable for tablet manufacture are acceptable. Such excipients include inert diluents such as calcium carbonate, sodium carbonate, lactose, calcium phosphate or sodium phosphate, granulating and disintegrating agents, such as corn starch or alginic acid, binding agents such as starch, gelatin or acacia; and lubricating agents such as magnesium stearate, stearic acid or talc. Tablets may be uncoated or may be coated by known techniques to delay disintegration and absorption in the gastrointestinal tract and thereby provide a sustained action over a longer period of time. For example, a time delay material such as glyceryl monostearate or glyceryl distearate alone or with a wax may be employed. The use of enteric coating is also contemplated.

Formulations for oral use may also be presented as hard gelatin capsules wherein the active ingredient is mixed with an inert solid diluent, for example calcium carbonate, calcium phosphate or kaolin, or as soft gelatin capsules wherein the active ingredient is mixed with water or an oil medium, such as peanut oil, liquid paraffin or olive oil.

Aqueous suspensions may contain the powder of the invention in admixture with excipients suitable for the manufacture of aqueous suspensions. Such excipients include suspending agents, dispersing or wetting agents, one or more preservatives, one or more coloring agents, one or more flavoring agents and one or more sweetening agents such as sucrose or saccharin.

Oil suspensions may be formulated by suspending the active ingredient in a vegetable oil, such as arachis oil, olive oil, sesame oil or coconut oil, or in a mineral oil such as liquid paraffin. The oil suspension may contain a thickening agent, such as beeswax, hard paraffin or cetyl alcohol. Sweeting agents, such as those set forth above, and flavoring agents may be added to provide a palatable oral preparation.

These compositions may be preserved by an added antioxidant such as ascorbic acid. Dispersible powders and granules of the invention suitable for preparation of an aqueous suspension by the addition of water provide the active ingredient in admixture with a dispersing or wetting agent, a suspending agent, and one or more preservatives. Additional excipients, for example, sweetening, flavoring and coloring agents may also be present. Syrups and elixirs may be formulated with sweetening agents, such as glycerol, sorbitol or sucrose. Such formulations may also contain a demulcent, a preservative, a flavoring agent and/or a coloring agent. The powder may be mixed with other ingestible forms and consumed in solid, semi-solid solution, suspension or emulsion form. It may also be mixed in conjunction or alternatively with pharmaceutically carriers, flavor enhancers, water, suspending agents and emulsifying agents. In a preferred embodiment, the powder is mixed with a citrus juice such as orange, grapefruit or tangerine due to the promotion of connective tissue formation by ascorbic acid. In a preferred essence, the powder may also be formulated in admixture with ascorbic acid.

For use as a nutritional dietary supplement, prophylactic or therapeutic agent, the powder is orally administered in a daily dosage. For dogs less than 50 pounds, for use as a nutritional dietary supplement, prophylactic or therapeutic agent, kolla2® is orally administered in powder, capsule or tablet form, in a daily dosage of between about 100 mg and 10,000 mg. More preferably, it is administered in a daily dosage of between about 500 mg and 4000 mg. Most preferably, it is administered in a daily dosage 700 mg and 1000 mg. For dogs above 50 pounds, for use as a nutritional dietary supplement, prophylactic or therapeutic agent, kolla2® is orally administered in powder, capsule or tablet form, in a daily dosage of between about 500 mg and 10,000 mg. Most preferably, it is administered in a daily dosage between about 700 mg. and 4000 mg. Most preferably, it is administered in a daily dosage between about 1,400 and 3000 mg.

For horses, for use as a nutritional dietary supplement, prophylactic or therapeutic agent, the inventive powder is also orally administered in a daily dosage generally based on the weight of the animal. For each 100 pounds of animal weight, a preferred dose is from about 100 mg to about 10,000 mg. Alternatively, and more preferably, the daily dose is about 500 mg. to about 3,000 mg. per 100 pounds of animal weight. And still alternatively a most preferred daily dose is from about 1000 mg. to about 2,500 mg.

The preferred embodiment, the supplement is taken on an empty stomach with vitamin C, or the kolla2® powder is mixed with water or a citrus juice prior to ingestion. The preparations described above can be taken indefinitely by dogs or horses affected by connective tissue disorders or by healthy animals as a preventative agent.

The above detailed description of the invention is set forth solely to assist in understanding the invention. It is to be understood that variations of the invention, including all equivalents now known or later developed are to be considered as falling within the scope of the invention, which is limited only by the following claims. 

1. A method of preparing Kolla2 powder for oral administration as a dietary supplement to a K9 or equine animal which comprises, separating at lease one member of the group consisting of cartilage derived from warm-blooded animals containing partially water-soluble, denatured Collagen Type II protein and subdividing such cartilage into dose amounts for therapeutically effective levels.
 2. The method of claim 1 wherein said Kolla2 powder has an average molecular weight of about 50,000 daltons.
 3. The kolla2 of claim 2, wherein said kolla2 is extracted from desiccated avian sternal cartilage and avian cartilage collagen type II protein.
 4. A method of positively influencing cartilage production and growth in a K9 or equine animal with a joint disorder, comprising orally administering to said animal an effective daily cartilage-inducing amount of kolla2.
 5. The method of claim 4, wherein said connective tissue disorder is selected from the group consisting of degenerative joint diseases, joint defects, hip displasia, and osteoarthritis.
 6. The method of claim 4, wherein for a K9 less than 50 pounds said effective daily dosage amount is between about 100 mg and 10,000 mg.
 7. The method of claim 4, wherein for a K9 less than 50 pounds said effective daily dosage amount is between about 500 mg and 4,000 mg.
 8. The method of claim 4, wherein for a K9 less than 50 pounds said effective daily dosage amount is between about 700 mg and 1,000 mg.
 9. The method of claim 4, wherein for a K9 weighing more than 50 pounds said effective daily dosage amount is between about 500 mg and 10,000 mg.
 10. The method of claim 4, wherein for a K9 weighing more than 50 pounds said effective daily dosage amount is between about 700 mg and 4,000 mg.
 11. The method of claim 4, wherein for a K9 weighing more than 50 pounds said effective daily dosage amount is between about 1,400 mg and 3,000 mg.
 12. The method of claim 4, wherein for a horse, for each 100 pounds of body weight, said effective daily dosage amount is between about 100 mg and 10,000 mg.
 13. The method of claim 4, wherein for a horse, for each 100 pounds of body weight, said effective daily dosage amount is between about 500 mg and 3,000 mg.
 14. The method of claim 4, wherein for a horse, for each 100 pounds of body weight, said effective daily dosage amount is between about 1000 mg and 2,500 mg.
 15. A method of daily nutritional supplement of kolla2 as a preventative for degenerative joint disease in a K9 or equine animal, comprising orally administering to an individual a daily dosage of kolla2 having an average molecular weight of between about 45,000 and 65,000 daltons.
 16. A method for treating an animal, such as a dog or horse having a degenerative joint disorder comprising administering to said animal a composition comprising collagen type II and having an average molecular weight of between about 45,000 and 65,000 daltons.
 17. The method of claim 16 wherein the composition is in powder form.
 18. The method of claim 16 wherein said connective tissue disorder is selected from the group consisting of degenerative joint diseases, joint defects, hip displasia, osteoarthritis, polychondritis, and menier's disease.
 19. The method of claim 16, wherein for a K9 less than 50 pounds said effective daily dosage amount is between about 100 mg and 10,000 mg.
 20. The method of claim 16, wherein for a K9 less than 50 pounds said effective daily dosage amount is between about 500 mg and 4,000 mg.
 21. The method of claim 16, wherein for a K9 less than 50 pounds said effective daily dosage amount is between about 700 mg and 1,000 mg.
 22. The method of claim 16, wherein for a K9 weighing more than 50 pounds said effective daily dosage amount is between about 500 mg and 10,000 mg.
 23. The method of claim 16, wherein for a K9 weighing more than 50 pounds said effective daily dosage amount is between about 700 mg and 4,000 mg.
 24. The method of claim 16, wherein for a K9 weighing more than 50 pounds said effective daily dosage amount is between about 1,400 mg and 3,000 mg.
 25. The method of claim 16, wherein for a horse, for each 100 pounds of body weight, said effective daily dosage amount is between about 100 mg and 10,000 mg.
 26. The method of claim 16, wherein for a horse, for each 100 pounds of body weight, said effective daily dosage amount is between about 500 mg and 3,000 mg.
 27. The method of claim 16, wherein for a horse, for each 100 pounds of body weight, said effective daily dosage amount is between about 1000 mg and 2,500 mg. 